Δ 9-Tetrahydrocannabinol-induced changes in prenatal growth and development of mice

Abstract

Delta-9-tetrahydrocannabinol (THC) administered ip in 10% Tween 80 and saline to pregnant Swiss-Webster mice produced a significant incidence of in utero deaths, reduction of body size, and offspring with cleft palate. The embryocidal and fetocidal effects are related to both dosage and day of administration. THC, 50 mg/kg, administered during early organogenesis produced 49% resorptions, while the same dosage administered during late organogenesis produced no significant increase in fetal resorptions. This gestational period susceptibility can be obviated if the in utero organism is exposed acutely on individual gestational days, or chronically during the entire period of organogenesis. Single dosages of THC, 300 mg/kg, produced 77 and 78% fetal resorptions when administered on gestational Days 8 or 16, respectively. THC administered to pregnant mice significantly reduced the body weight of surviving fetuses. THC, 50 mg/kg, administered on gestational Days 10 and 11 reduced the mean fetal body weight by about 15% when compared to corresponding controls. The period of greater susceptibility to growth retardation actions was during gestational Days 10–16. Variations of female percentage of body weight gains were not significantly different from control groups. Examination of skeletal development showed no anomalies. THC produced offspring with cleft palate. Single dosages of THC, 300 mg/kg, produced 50 and 30% incidence of cleft palate when administered on gestational Days 12 or 14, respectively. Cleft palate occurred after multiple dosages of THC at 75, 80, and 100 mg/kg.